An Embryonic Test Tube to Assay The Function of Drosophila Morphogens

早期果蝇胚胎有几种形态发生梯度。通过特定激活的合子基因，指导沿前后轴的适当发育，形成头部、胸部和腹部的双头形状。然而，至少有另外两个系统——驼背（hb）和尾侧（cad）——似乎在胚胎中也起着重要作用。这两个基因可能代表了昆虫的祖先模式系统，其功能部分被果蝇的Bicoid所取代。揭示这些基因作用的问题之一是不同母系之间的高度冗余和交叉相互作用。我们建议分析胚胎中每个系统的形态发生特性，这些系统完全响应这些分子的模式，但与其他母体系统的所有潜在相互作用/冗余已被消除。这种“胚胎试管”的构建要求我们从基因上移除所有母体模式系统（通过产生生殖系在双头体、驼背体、尾状体、纳米体、末端和背-腹侧通路上突变的果蝇）。在这种背景下，我们将为每个要测试的形态素提供人工梯度。我们将首先关注Bicoid， Hunchback和Caudal的作用。由于这些系统之间的相互作用，目前尚不清楚Bcd是否单独发挥作用，以及Hb和Cad的形态发生作用是什么。我们还将测试纳米和终端系统对胚胎的塑造能力。作为这项工作的延伸，我们将测试其他被提出作为形态因子的分子的作用，特别是间隙基因产物以及分泌分子，如Dpp， Wg和Hh。到目前为止，这些分子的功能已经在广泛的预模式已经存在的情况下进行了分析。这项工作将为关键模式分子在细胞事件中的直接作用提供见解，这些细胞事件导致胚胎或更广泛地说，在其他组织中确定位置值。

Several morphogenetic gradients have been shown to pattern the early Drosophila embryo. Bicoid patterns head, thorax and abdomen through the specific activation of zygotic genes that direct proper development along the antero-posterior axis. However at least two other systems hunchback (hb) and caudal (cad), appear to also play important roles in the embryo. These two genes may represent the ancestral patterning system of insects whose function has been partially taken over by Bicoid in Drosophila.One of the problems in uncovering the role of these genes is the high level of redundancy and of cross-interactions among the different maternal systems. We propose to analyze the morphogenetic properties of each system in an embryo that is fully responsive to patterning by these molecules, but where all potential interactions/redundancy with the other maternal systems have been eliminated. Construction of this 'embryonic test tube' requires that we genetically remove all maternal patterning systems (by generating flies whose germline is mutant for bicoid, hunchback, caudal, nanos, the terminal and dorso-ventral pathways). In this background, we will provide artificial gradients for each morphogen to be tested. We will first focus our attention on the role of Bicoid, Hunchback and Caudal. Because of the cross-interactions among these systems, it is still unclear whether Bcd has any role on his own, and what the morphogenetic roles of Hb and Cad are. We will also test the ability of Nanos and the terminal system to pattern the embryo. As an extension of this work, we will test the role other molecules that have been proposed to act as morphogens, in particular the gap genes products as well as secreted molecules such as Dpp, Wg and Hh. The function of these molecules has so far been analyzed in situations where an extensive pre-pattern already exists.This work will provide insights into the direct role of critical patterning molecules on cellular events that lead to the determination of positional values in the embryo or, more generally, in other tissues.